New paths to important building blocks
Catalysis is critically important to industrial chemistry, speeding the rate and thus yield of product in a given amount of time. Catalysts do so without actually being consumed themselves in the reactions so they can be used again and again. They act somewhat like matchmakers, bringing reactants closer physically, energetically or both to help nature take its course. Addition reactions in which two or molecules combine form an important class of compounds. Enantioselective catalysts with two binding sites for simultaneous activation of the two reactants (cooperative catalysis) can facilitate efficient reactions with low concentrations of catalyst and are thus industrially sought after. EU-funded scientists developed new catalysts for a specific addition reaction of interest within the context of the project 'Enantioselective isocyanoacetate addition reactions under cooperative base and Lewis acid catalysis' (ENISOCOC). Imidazolines are at the core of many biologically active compounds and are building blocks for many others. Asymmetric synthesis of 2-imidazolines has been the focus of much research, in particular via a direct route. However, a much more challenging reaction has not been addressed despite its great potential as a unique path to specialised 2-imidazolines. The team explored a new binary catalyst system and its capability for new reactivity and absolute and relative stereocontrol in reactions where previously there was no precedent. In particular, scientists studied the catalytic asymmetric Mannich-type addition/cyclisation of isocyanoacetate pronucleophiles I with ketimines II to yield imidazolines III. Extensive experimentation assessed various solvents, electron donors and acceptors, reaction conditions and precatalysts, and effects on product yield and enantioselectivity. ENISOCOC successfully demonstrated an efficient and general method for synthesising highly functionalised 2-imidazolines, very important compounds in the synthetic pathway toward many biologically active molecules. The reactions are of great interest to the field of catalysis. The unique pathways to biologically relevant molecules will aid numerous applications as well.
Catalytic systems, synthetic chemistry, catalysts, addition reactions, enantioselective, cooperative catalysis, imidazolines, biologically active molecules